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DOI: 10.1055/s-0036-1592257
Why do some adults with PiMZ alpha1-antitrypin develop bronchiectasis?
Several reports indicate an association among inherited alpha-1-antitrypsin deficiency (A1ATD), pulmonary infections and bronchiectasis. Most reported A1ATD cases with bronchiectasis are elderly homozygous PiZZ (Glu342Lys) smokers with emphysema. Whether there is an increased risk of pulmonary diseases, including bronchiectasis, in heterozygous PiMZ A1ATD carriers is debated.
We describe an 18-year old, non-smoking male who had neonatal hyperbilirubinemia and suffered from productive cough, chronic rhinosinusitis and recurrent otitis since early childhood. A high-resolution CT scan of the chest revealed bronchiectasis in both lower lobes with thickening of bronchial walls and additional tree-in-bud sign, indicating bronchiolitis and mucus plugging, but no emphysema. Analysis of the serum A1AT and phenotyping revealed that this patient had reduced A1AT levels of 0.78 g/L (normal is 0.9 – 2.0 g/L) associated with an intermediate PiMZ A1ATD. To elucidate a possible link between PiMZ A1ATD and bronchiectasis, we asked whether blood neutrophils and A1AT protein isolated from our PiMZ patient differ from healthy PiMM donors. At a baseline and in response to inflammatory stimuli PiMZ neutrophils expressed more elastase and IL-1β and less A1AT than PiMM neutrophils. Moreover, affinity purified MZ A1AT protein had lower ability to inhibit endotoxin-induced TNFα and IL-1β expression than MM A1AT. Our findings in a young patient highlight the quantitative and qualitative deficiency of MZ A1AT, which offers an explanation for the early-age airways infections and early-age onset of bronchiectasis.